Age-related macular degeneration (“AMD”), a progressive retinal disease, is the leading cause of blindness, particularly among patients over 65 years old. In the U.S., approximately 15 million patients are affected by AMD, and the prevalence of this disease among elder patients increases exponentially in the last decade. Patients with AMD experience gradual worsening of vision and eventually develop blurred or no vision in the central area of the visual field (or the macular). Exudative neovascular (wet form) and non-neovascular (dry form) are two major kinds of AMD. While macula thinning and pigmentation disturbance are observed in dry form, wet form is often associated with abnormal blood vessels growing under retina and macula. Vision deterioration caused by wet form progresses more rapidly than dry form. Wet form, characterized by choroidal neovascularization (CNV), leads to 80% to 90% of severe vision loss associated with AMD.
Vascular endothelial growth factor (VEGF) inhibitors are commonly used for treating AMD and a wide variety of other retinal diseases, e.g., diabetic retinopathy, retinal vein occlusions (RVOs), neovascular glaucoma, retinopathy of prematurity (ROP), and intraocular tumors. Intravitreal injection of VEGF inhibitors (bevacizumab, pegaptanib, ranibizumab, or aflibercept) has shown its efficacy in treating wet AMD.
However, intravitreal injection of VEGF inhibitors poses the risk of post-injection- and drug-class-associated adverse events. The incidence of infectious endophthalmitis per patient was reported in ranges from 0.019 to 1.6%. See Scott et al., Retina, 27: 10-12 (2007). Intravitreal injection of VEGF inhibitors is also associated with intraocular inflammation, rhegmatogenous retinal detachment, intraocular pressure elevation, and ocular hemorrhage. Falavarjani et al., Eye, 27, 787-794 (2013). The monthly injections and clinical assessment necessitated by anti-VEGF therapy impose additional drain on patients and clinicians required to follow a stringent, tedious treatment regime.
For CNV, there has not been an effective, proven therapy. Though laser photocoagulation may be used in limited population to remove CNV, the procedure can also affect the viable photoreceptors overlying the visual area affected by CNV, resulting in immediate visual acuity loss. Photodynamic therapy may avoid the side effect on the overlying visual area, but patients treated by photodynamic therapy often experience elevated intra-ocular pressure and sensitivity to light for days.
These highlight a need for a more effective, easily administration method or pharmaceutical composition for treating ocular diseases (e.g., AMD and CNV) or for delaying or reversing onset of the vision loss and/or blurring caused by the ocular diseases.